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  • 1
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    A Phase II Study of Dasatinib in Patients with Chronic Myeloid Leukemia (CML) in Myeloid Blast Crisis Who Are Resistant or Intolerant to Imatinib: First Results of the CA180006 ‘START-B’ Study. (2005)
    American Society of Hematology
    Details
    Publication Date: 2005-11-16
    Description: Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases. Data from a phase I study suggest that dasatinib exhibits potent activity with high hematologic and cytogenetic response rates in CML patients with myeloid blast crisis (MBC) who were imatinib (IM)-resistant (IM-R) or -intolerant (IM-I). Here we report the preliminary results from one Phase II trial (Study CA180006 or ‘START-B’) in MBC, which was initiated in December 2004. This open-label study was carried out in 37 centers worldwide between December 2004 and May 2005. A total of 74 IM-R or IM-I MBC pts were accrued (41 male, median age 56 years [range 21–71]). Preliminary data are currently available on the first 34 pts (29 IM-R and 5 IM-I). Dasatinib was administered orally, at a dose of 70 mg twice daily (BID) in a continuous daily dosing schedule; dose escalation to 100 mg BID was permitted for patients who did not achieve hematologic response and dose reduction to 50 mg and 40 mg BID was allowed in the presence of persistent toxicity. Complete blood counts were performed weekly and bone marrow assessment, including cytogenetic analysis, was performed monthly. Mutations in the BCR-ABL domain were assessed in all pts. Pretreatment characteristics of these 34 pts included: 71% male, median age 54 years (range 21 – 71). Median duration of CML from first diagnosis was 49.3 months (range 5.6 – 215.5). Prior therapy included bone marrow transplant (5 pts, 15%) and interferon (18 pts, 53%). In 44% of pts, the highest IM dose was 〉600 mg/day and 41% of pts received IM for 〉3 years. Best responses to IM were complete hematologic response (CHR) in 82% of pts and major cytogenetic response in 39% of pts (complete in 27%, and partial in 12%). At baseline, 35% of pts had a WBC count ≥20 x 103/mm3, 71% had a platelet count
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 2
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    Flow Cytometry Study of CD148, a Tyrosine Phosphatase Receptor, in 184 Chronic B Cell Malignancies, Reveals a High Expression in Mantle Cell and Marginal Zone Lymphomas. (2009)
    American Society of Hematology
    Details
    Publication Date: 2009-11-20
    Description: Abstract 1923 Poster Board I-946 We recently characterized CD148 as a potential marker for mantle cell lymphoma using mass spectrometry analysis of cell-derived microvesicles in a restricted set of patients (ASH Annual Meeting Abstracts, Nov 2008; 112: 1766). CD148 is a plasma membrane receptor with phosphatase activity related to CD45, composed of an extracellular domain containing 8 fibronectin type II-like domains, a transmembrane region and a single intracellular phosphatase domain. Interestingly, it was recently shown that deletion of the phosphatase domain of CD148 in mice blocks B cell development at the transitional stage, with a dramatic increase of marginal zone B cells. BCR signalling events are also substantially altered in CD148/CD45 doubly deficient mice. In the present study, we analyzed the expression of CD148 using flow cytometry in a larger group of controls and patients with circulating pathologic B-cells, including 93 chronic lymphocytic leukemia (CLL), 46 small lymphocytic lymphomas with Matutes score inferior or equal to 3 (SLL), 35 MCL, all harboring (11;14) translocation and/or cyclin D1 overexpression, 5 marginal zone lymphomas (MZL), 5 splenic lymphoma with villous lymphocytes (SLVL), as well as 30 controls. Mean fluorescence intensity of direct CD148 staining with phycoerythrin conjugated 143−41 clone was used for expression comparison. CD148 MFI of the 30 control cells was weak and very homogeneous (mean = 168, SD = 31), as well as in the 93 CLL (mean = 199, SD = 84). SLL cases (n=46) were stained slightly higher (mean = 297, SD = 138) revealing a slight but significant difference with CLL (p
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
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